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Results for “Collagen Type IV”

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At least 19 recordsLinked to original sources
PubMed1979

Immunochemical study on basement membrane (type IV) collagens.

Basement membrane (type IV) collagens were extracted from a mouse tumour with acetic acid and from human placenta after limited enzymatic digestion. Antisera were produced against both collagens in rabbits and guinea-pigs and examined by various assays. These antisera were found to be specific for basement membrane collagen and showed little or no cross-reactions with the interstitial collagens, types I, II and III or with human placenta collagen consisting of alpha A and alpha B chains. Varying degrees of cross-reaction were observed between antisera to human and mouse type IV collagen. Immunochemical analyses demonstrated the presence of three distinct determinants in the tumour type IV collagen. Rabbit antisera against this antigen reacted with either collagenase-resistant segments or with a collagenous, disulphide-bonded segment (P3). Guinea-pig antisera recognized primarily antigenic determinants in the P3 segment. Antisera to placenta type IV collagen reacted with another collagenous, pepsin fragment (P1) which lacks disulphide bonds. These antisera showed complete cross-reaction with collagenous alpha 1 (IV) chains prepared from pepsin-digests of human placenta and bovine lens capsule.

Animals↗
PubMed1979

Immunofluorescence demonstration of type IV collagen and a noncollagenous glycoprotein in thickened vascular basal membranes in protoporphyria.

Specific rabbit antibodies to type IV collagen isolated from a basement membrane producing mouse tumor were used in indirect immunofluorescence tests to study the thickened vascular basement membrane in skin biopsies from patients with erythropoietic porphyria (EPP) and from protoporphyric mice. In addition, rabbit antibodies to a noncollagenous, basement membrane specific glycoprotein also derived from the mouse tumor were tested. It was shown that normal as well as altered vascular basement membranes in both the human and the murine skin specimens react with the anti-type IV collagen and the antiglycoprotein antibodies. A particular strong reaction in the diseases skin indicated that formation of new vascular basement membrane layers involved deposition of the major structural proteins which also constitute normal basement membrane matrices.

Animals↗
PubMed1978

Histochemical demonstration of type IV collagen in the renal glomerulus.

Disulfide-groups are demonstrated in the basement membranes of glomerular capillaries, proximal convoluted tubules, and collecting ducts by means of a thiosulfathion/Alcian Blue +0.8 Mol MgCl2-staining sequence. It is suggested that the reaction shows type IV collagen of basal lamina material, which is characterized by a relatively high cystine content (8 half-cystine residues/1000).

Animals↗
PubMed1979

Type IV and type "A-B" collagens do not elicit platelet aggregation or the serotonin release reaction.

Human collagens were isolated from kidney, lung, skin, aorta, cartilage, and placenta. Five different types were obtained, including two new molecular species, one characteristic of basement membranes, or type IV collagen, and the other the recently described "A-B" collagen derived from fetal membranes. All the collagens were purified and separated by combination of heat-gelation fractionation and salt fractionation. In neutral solution at 37 degrees neither type IV nor type "A-B" collagen elicited platelet aggregation or 14C-serotonin release. Preincubation of platelets with both types IV and "A-B" collagen did not inhibit aggregation upon subsequent addition of collagen types I, II, or III.

Aorta↗
PubMed1979

Hormonal requirements for basement membrane collagen deposition by cultured rat mammary epithelium.

Alveoli and ducts isolated from virgin rat mammary glands synthesize basement membrane collagen (typeIV) in primary culture. Using purified antibodies to type IV collagen, prominent intracellular and extracellular fluorescence is observed in the epithelium. No fluorescence is observed with antibodies to collagen type I and III. From quantitation of the incorporation of [14c]proline-labeled proteins, 1.5 to 2.5 per cent of the newly synthesized proteins are collagen. Type IV collagen from these cultures was biochemically identified on the basis of (1) the high ratio of labeled 3-hydroxyproline to 4-hydroxyproline (1:10), (2) the gel electrophoretic pattern of the collagenase-sensitive proteins precipitated with 1.7 M NaCl, (3)the failure of the collagen to bind to diethylaminoethyl-cellulose, and(4)the immunologic cross-reactivity with mouse tumor type IV is identical with that of type IV collagen from other sources. When the supportive hormones, insulin, prolactin, hydrocortisone, progesterone, and estradiol are removed from the cultures, there is a 90 per cent reduction in the amount of [3H]proline recovered in collagen synthesis coincides with only a 30 percentdrop in the growht rate and a 20 per cent drop in total protein synthesis of the sells over the 24-hour period without hormones. Pulse-chase experimout hormones. Pulse-chase experiments revealed an enhanced turnover of collagen following hormone withdrawal. This system may be an in vitro model of collagen turnover in mammary gland in involution.

Animals↗
PubMed1976

Rat parietal yolk sac basement membrane. An investigation of the antigenic determinants using a radioimmunoassay.

Previous studies have shown that there is microscopic and biochemical evidence that rat parietal yolk sac synthesizes basement membrane (type IV) collagen; this study shows that a radioimmunoassay may be used for the detection of type IV collagen in such biosynthetic systems. Rat parietal yolk sacs incubated in medium containing (14C) proline either with or without alphaalpha-dipyridyl produced either unhydroxylated or hydroxylated (14C)collagen. The immunological reactivity of these two preparations was investigated using antibodies to bovine type IV collagen in a radioimmunoassay which demonstrated that the hydroxylated (14C)collagen preparation had a considerably higher level of antigenicity than the unhydroxylated (14C)collagen. Hydroxylated rat type IV (14C)collagen which had been reduced and alkylated was intermediate in antigenicity between hydroxylated and unhydroxylated material. These findings suggest that there are antigenic determinants which depend upon hydroxylation of the collagen molecule, and others dependent upon intact disulphide bonds. In addition, various levels of pepsin extracted unlabelled calf anterior lens capsule collagen caused inhibition of antibody binding to (14C)collagen. Rat type IV (14C)collagen which had been digested with collagenase was inactive in the radioimmunoassay, while pepsin digestion caused no reduction in antigenicity. These findings suggest that the antiserum is directed towards the collagenous part of the molecule and may be a useful tool in the detection of biosynthesized basement membrane collagen.

Alkylation↗
PubMed2025

Splice modulation of COL4A5 reinstates collagen IV assembly in an organoid model of Alport syndrome.

Kidney organoids are an emerging tool for disease modeling, especially genetic diseases. Among these diseases, X-linked Alport syndrome (XLAS) is a hematuric nephropathy affecting the glomerular basement membrane (GBM) secondary to pathogenic variations in the COL4A5 gene encoding the α5 subunit of type IV collagen [α5(IV)]. In patients carrying pathogenic variations affecting splicing, the use of antisense oligonucleotides (ASOs) offers immense therapeutic hope. In this study, we develop a framework combining the use of patient-derived cells and kidney organoids to provide evidence of the therapeutic efficacy of ASOs in XLAS patients. Using multiomics analysis, we describe the development of GBM in WT and mutated human kidney organoids. We show that GBM maturation is a dynamic process, which requires long organoid culture. Then, using semi-automated quantification of α5(IV) at basement membranes in organoids carrying the splicing variants identified in patients, we demonstrate the efficacy of ASO treatment for α5(IV) restoration. These data contribute to our understanding of the development of GBM in kidney organoids and pave the way for a therapeutic screening platform for patients.

Nephritis, Hereditary↗
PubMed1978

Localization of the collagenous component in skin basement membrane.

Antibodies to type IV collagen were produced by immunizing rabbits with a basement membrane collagen obtained from a transplantable mouse tumor. Using specifically purified antibodies, type IV collagen was localized ultrastructurally to the basal lamina part of the basement membrane zone.

Animals↗
PubMed1976

The use of the radioimmunoassay in the characterization of antibodies to basement membrane collagen.

This study describes the use of the radioimmunoassay for the characterization of antibodies to basement membrane (type IV) collagen from bovine anterior lens capsule. The immunogen was extracted from calf anterior lens capsules by limited pepsin digestion and injected into rabbits. The antisera were characterized using gel diffusion, haemagglutination and the radioimmunoassay in which 125I-labelled types I, II, III, and IV bovine collagen were employed. In the direct radioimmunoassay there was no reaction with either native or denatured types I, II or III bovine collagen, whereas there were high titres towards both native and denatured type IV bovine collagen. Radioimmune inhibition studies using unlabelled types I, II, III and IV bovine collagen, collagenase digested and repepsinized type IV collagen showed that there was marked inhibition by either native, denatured or repepsinized type IV collagen, and slight inhibition by native type I collagen; native type II and type III, denatured types I, II and III, and collagenase digested type IV collagen had no inhibitory effects.

Amino Acids↗
PubMed1979

Isolation and characterization of a native placental basement-membrane collagen and its component alpha chains.

Native type IV collagen was isolated from human placenta using pepsin solubilisation followed by fractional salt precipitation and chromatogarphic purification. The native preparation was characterised using amino acid analyses, disc gel electrophoresis, segment-long-spacing crystallites and immunological methods. Two component alpha chains were isolated with molecular weights of approximately 95000 and 70000. Cyanogen bromide digests of these chains indicated that they are not related to any of the known alpha chains of interstitial collagens or to the recently described collagen containing alphaA and alphaB chains. They are also not related to one another and are therefore probably fragments of two genetically distinct type IV collagen alpha chains.

Amino Acids↗
PubMed2024

Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient. METHODS: We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R). RESULTS: We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same. CONCLUSIONS: Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.

Humans↗
PubMed1979

[Biochemical studies on collagen and connectin from human skeletal muscle: age-related changes in the properties of elasticity (author's transl)].

Collagen and connectin, an intracellular elastic protein, play important roles in structural maintenance and mechanical continuity of skeletal muscle. The author has investigated age-related changes in these proteins from human skeletal muscles ranged from 6 lunar month to 79 years of age. The total content of collagen in skeletal muscle at 6 lunar month was 1.7% of wet weight of the tissue. This value was found to decrease to 0.8% by 5 years of age, and no significant change in this value was observed after 5 years of age. Collagen in skeletal muscle tissue was found to consist of 80% of Type I collagen, 19% of Type III collagen and 1% of Type IV collagen. The proportion of these genetically distinct types of collagen was constant throughout the whole life-span. The amount of soluble collagen and formation of reducible cross-links of collagen were found to decrease with age. Although the content of connection in skeletal muscle from human embryo was low, 0.9-1.1% of wet weight of the tissue, it gradually increased to 2.9% at 79 years of age. Following NaB3H4 reduction, connectin was found to contain the reducible cross-links derived from lysine- and hydroxylysine-aldehydes; two of them were identified as lysinonorleucine and histidino-hydroxymerodesmosine, and additional three reducible compounds were eluted between elution positions of dihydroxylysinonorleucine and lysinonorleucine from ion exchange chromatography. These findings strongly indicate that connectin and connective tissue proteins, collagen and elastin, share common features of cross-linking. Furthermore, these reducible cross-links were found to decrease with age. Thus, maturations of both connectin and collagen are apparently due to qualitative changes in their reducible cross-links.

Adolescent↗
PubMed1978

Histochemical demonstration of disulfide-groups in the lamina propria of human seminiferous tubules.

The distribution of disulfide-groups was investigated in the tunica propria of human seminifersou tubules by means of a thiosulfation/Alcian Blue + 0.8 Mol MgCl2-staining reaction. Controls had shown the absence of significant amounts of sulfhydryl- or sulfate-groups in the lamina propria, which groups would also be demonstrated by the method employed. The lamina propria of human seminiferous tubules is rich in disulfide groups. The staining reaction decreases in the region of the tubulus rectus, is only faint in the connective tissue which underlies the epithelium of the rete testis, and is absent in the lamina propria of efferent ducts. It is suggested that microfibrils and type IV collagen (both rich in cystine) are the materials responsible for the histochemical reaction described. The occurrence of multiple layers of basal lamina material (type IV collagen) and bundles of microfibrils is shown in comparative electron microscopic studies.

Disulfides↗
PubMed1979

Platelet-reactivity of isolated constituents of the blood vessel wall.

Collagens I and III, in fibrillar form, bound platelets equally well; both readily induced platelet aggregation. In contrast, collagens IV and V, although pretreated as collagens I and III to induce fibrillogenesis, failed to produce aggregation. No binding of platelets was detected. Lens capsule, containing collagen type IV in situ, was also inactive. Inactivity appears due to the lack of an appropriate quaternary structure since segment-long-spacing (SLS) aggregates of collagens IV and V, as of type I, induced aggregation. Elastin and its associated microfibrillar element did not aggregate platelets; some binding of platelets to elastin only was observed.

Animals↗